舒尼替尼阻断STAT3 通路抑制头颈癌细胞PCI-13 增殖.docVIP

舒尼替尼阻断STAT3通路抑制头颈癌细胞PCI-13增殖 贾志宇1，赵云转1，屈鹏飞1，张英怀1，Lim Chweeming2，Robert L Ferris2 （050000，河北医科大学第二医院口腔颌面外科1；15213宾夕法尼亚州，美国匹兹堡大学医学院耳鼻咽喉-头颈外科2） [摘要] 目的 体外研究舒尼替尼对头颈癌细胞系PCI-13增殖和凋亡的影响，并观察STAT1、STAT3在凋亡过程中的变化，探讨STAT3通路在舒尼替尼诱导肿瘤细胞凋亡中的作用。方法 体外培养PCI-13细胞，用不同浓度的舒尼替尼处理24、48、72h后，应用MTT比色实验，倒置显微镜、Wright-Giemsa染色、流式细胞术检测和观察PCI-13的生长抑制率和凋亡情况。细胞经血清饥饿后，分别用0、1、2、4μmol/L的舒尼替尼处理2、8、16和24h，采用流式细胞术检测p-STAT1和3的表达，并设阴性和阳性对照组。结果 舒尼替尼可明显抑制PCI-13细胞的增殖，其最高抑制率可达92%，抑制率呈时间-浓度依赖性。同时舒尼替尼可诱导PCI-13细胞凋亡，凋亡率随处理时间延长和药物浓度增加而上升。舒尼替尼不影响p-STAT1的表达，但是可以显著抑制p-STAT3的表达，这种抑制存在浓度依赖性。结论 舒尼替尼不但能够抑制PCI-13细胞增殖，诱导其凋亡，而且能够抑制PCI-13细胞中STAT3的磷酸化水平，减少其激活。提示舒尼替尼诱导PCI-13细胞凋亡可能由STAT/JAK途径介导。 [关键词] 舒尼替尼；头颈癌；增殖；凋亡；信号转导和转录激活因子3 [中图法分类号] [文献标志码] A [通信作者] ，E-mail： Sunitinib could inhibit the proliferation of head and neck cell line PCI-13 by blocking the STAT3 signal pathway Jia Zhiyu, Luo Fengyu, Zhao Yunzhuan, et al.　 (1Department of Oral and Maxillofacial Surgery, Second Hospital of Hebei Medical University, Shijiazhuang,Hebei Province,050000,China; 2 ) [Abstract] Objective To evaluate effect of sunitinib on proliferation and expression of phosphorylating- signal transducer and activator of transcription1 and 3 (STAT1，STAT3) of the head and neck cancer cell line PCI-13 in vitro, to explore the role of STAT3 pathway in the antitumor activity of sunitinib. Methods PCI-13 cells were treated with different concentration of sunitinib for 24, 48h and 72h. Then MTT assay, inversion phase contrast microscope, Wright-Giemsa staining and flow cytometry were used to calculate the growth inhibition rate and to observe the apoptosis of PCI-13. PCI-13 cells were respectively treated with 0，1，2 and 4μmol/L sunitinib for 2, 8, 16 and 24h after 48h sera starving in vitro. And positive controls were set. Then phosphorylated-STAT1 and 3 were detected with flow cytometry. Results Sunitinib could inhibit the growth of PCI-13 significantly in a time and concentration-dependent manner and the highest inhibition rate was